Multifunctional 2-bit coded reconfigurable metasurface based on graphene-vanadium dioxide.

In this paper, a graphene-vanadium dioxide-based reconfigurable metasurface unit structure is proposed. Using the change at a graphene Fermi energy level on the surface of the unit structure to satisfy the 2-bit coding condition, four reflection units with a phase difference of 90 ∘ can be discovered. The modulating impact of the multi-beam reflection wave with 1-bit coding is then confirmed. Then we study the control of a single-beam reflected wave by metasurfaces combined with a convolution theorem in a 2-bit coding mode. Finally, when vanadium dioxide is in an insulating condition, the structure can also be transformed into a terahertz absorber. It is possible to switch between a reflection beam controller and a terahertz multifrequency absorber simply by changing the temperature of the vanadium dioxide layer without retooling a new metasurface. Moreover, compared with the 1-bit coded metasurface, it increases the ability of single-beam regulation, which makes the device more powerful for beam regulation.

High-Q multiple Fano resonances with near-unity modulation depth governed by nonradiative modes in all-dielectric terahertz metasurfaces.

Reducing radiative losses for a high quality factor resonance based on the concept of nonradiative states including anapole mode and bound states in the continuum mode has been attracting extensive attention. However, a high quality factor resonance is obtained at the expense of its modulation depth. Here, an asymmetric metasurfaces structure consisted of silicon double D-shaped resonator arrays that can support both an anapole mode and two bound states in the continuum modes in terahertz band is proposed, which has not only ultrahigh quality factor but also near-unity modulation depth. A resonance derived from anapole mode with stronger electromagnetic field enhancement and higher quality factor can be achieved by increasing the gap of resonator. Meanwhile, two Fano resonances governed by bound states in the continuum modes can be identified, and their quality factors can be easily tailored by controlling the asymmetry of resonator. Such an all-dielectric metasurfaces structure may give access to the development of the terahertz sensors, filters, and modulators.

Terahertz determination of imidacloprid in soil based on a metasurface sensor.

Pesticides in soil are continuously one of the most studied analytes due to their environmental and human health effects. Thus the detection of pesticides in soil is an important means to control and assess soil quality. Here, we theoretically and experimentally present a novel method for the determination of imidacloprid in soil by using a metasurface sensor operating at terahertz frequencies. The metasurface shows a resonance peak at 880 GHz and the electric field at the peak is strongly localized and concentrated in the gap of split I-shaped resonator. The detection of complex refractive index shows that the position and the transmittance of resonance peak are depend on the change in the complex refractive index. The measurement of imidacloprid concentration in soil demonstrates that both the frequency shift and the transmittance change at peak increase almost linearly with the increasing of imidacloprid concentration ranging from 0.25% to 2%. In this case, the frequency shift reaches 97 GHz and the transmittance change at peak is as high as 30.9%. Our work enables the determination of imidacloprid in soil at terahertz frequencies with good reliability and high sensitivity, showing the potential application of terahertz spectroscopy in environmental monitoring.

Graphene electromagnetically induced transparent polarization-insensitive sensors in the mid-infrared frequency band.

In this paper, a polarization-insensitive sensor based on graphene electromagnetically induced transparency (EIT) is proposed. The device consists of two graphene orthogonal T-shaped structures. This T-shaped resonator produces transparent windows that largely overlap under x and y polarizations, and the results demonstrate its good polarization insensitivity. The device can accomplish detection performance with sensitivity higher than 4960 nm/RIU and figure of merit (FOM) greater than 11.4. Meanwhile, when the Fermi energy level of graphene changes from 0.5 to 0.8 eV, it enables arbitrary modulation of the operating frequency over a wide frequency range of about 4.5 terahertz in the mid-infrared band. Our work has the potential to significantly advance the area of biological molecular detection.

Pharmaceutical Cocrystals of Ethenzamide: Molecular Structure Analysis Based on Vibrational Spectra and DFT Calculations.

Pharmaceutical cocrystals can offer another advanced strategy for drug preparation and development and can facilitate improvements to the physicochemical properties of active pharmaceutical ingredients (APIs) without altering their chemical structures and corresponding pharmacological activities. Therefore, cocrystals show a great deal of potential in the development and research of drugs. In this work, pharmaceutical cocrystals of ethenzamide (ETZ) with 2,6-dihydroxybenzoic acid (26DHBA), 2,4-dihydroxybenzoic acid (24DHBA) and gallic acid (GA) were synthesized by the solvent evaporation method. In order to gain a deeper understanding of the structural changes after ETZ cocrystallization, terahertz time domain spectroscopy (THz-TDS) and Raman spectroscopy were used to characterize the single starting samples, corresponding physical mixtures and the cocrystals. In addition, the possible molecular structures of ETZ-GA, ETZ-26DHBA and ETZ-24DHBA cocrystals were optimized by density functional theory (DFT). The results of THz and Raman spectra with the DFT simulations for the three cocrystals revealed that the ETZ-GA cocrystal formed an O-H∙∙∙O hydrogen bond between the -OH of GA and oxygen of the amide group of the ETZ molecule, and it was also found that ETZ formed a dimer through a supramolecular amide-amide homosynthon; meanwhile, the ETZ-26DHBA cocrystal was formed by a powerful supramolecular acid-amide heterosynthon, and the ETZ-24DHBA cocrystal formed the O-H∙∙∙O hydrogen bond between the 4-hydroxy group of 24DHBA and oxygen of the amide group of the ETZ molecule. It could be seen that in the molecular structure analysis of the three cocrystals, the position and number of hydroxyl groups in the coformers play an essential role in guiding the formation of specific supramolecular synthons.

Highly sensitive terahertz fingerprint sensing with high-Q guided resonance in photonic crystal cavity.

In order to solve the problem of low sensitivity and poor selectivity in biochemical sensing using terahertz technology, a new sensing scheme based on photonic crystal cavity structure is proposed. It is composed of two identical photonic crystal slabs, each of which consists of a square lattice of silicon-based cylindrical pillars on a silicon substrate. The geometric parameters of the cavity are optimized to obtain a guided resonance peak at 529.2 GHz with a high quality factor of 529. The detected object is located in the middle of cavity where the electric field is strongly localized and confined. The effective detection of lactose with only a few microns thick is taken as an example to demonstrate the sensing performance of this cavity. A distinct decrease in transmittance at resonance peak is observed. The sensitivity using our proposed cavity is 31 times higher than that of using a substrate. Moreover, the selectivity of this photonic crystal cavity for the target is also verified by using fructose as the non-target. These results show that the photonic crystal cavity has potential to be applied for fingerprint detection with high sensitivity as well as selectivity in terahertz sensing.

Planar antenna array as a highly sensitive terahertz sensor.

In this paper, a planar comb-shaped antenna array for terahertz sensing based on the excitation of spoof surface plasmon modes is proposed. The structure is constructed by an array of three periodic rectangular grooves perforated through metal stripes on top of a silicon substrate. The effective detection of lactose is given as an example to demonstrate the ability of this structure to enhance detection sensitivity. In transmission mode, the sensing signal of lactose using the antenna array was 7.6 times larger than that of using a silicon substrate. In reflection mode, the sensing signal of lactose increased almost 13 times using our proposed antenna array compared to that of using a silicon substrate, exhibiting high sensitivity in terahertz sensing. Further, lactose thickness could be predicted based on the reflectance at the peak using our proposed structure. Our results indicate that the proposed structure has great potentiality in the field of biological and chemical sensing.

Enhanced terahertz sensing with a coupled comb-shaped spoof surface plasmon waveguide.

A comb-shaped waveguide based on the excitation of coupled spoof surface plasmon (CSSP) mode is investigated, and is found to have a pronounced effect for the enhancement of fingerprint detection sensitivity in the terahertz (THz) regime. Composed of two oppositely oriented metal stripes with single-side comb-shaped corrugations, the waveguide is formed due to the coupling of SSP modes supported by metal corrugations on both sides and the mode is tightly localized between the central gap, which provides a perfect site for accommodating the samples in THz sensing. The effective detection of thin-layer lactose is given as an example to demonstrate the sensitive detection of it at a thickness of only a few microns. A transmission spectrum through the waveguide with a pronounced dip at its characteristic absorption frequency of 0.529THz is shown, which can never be observed using the transmission through a lactose layer with the same thickness.

Feasibility of terahertz time-domain spectroscopy to detect tetracyclines hydrochloride in infant milk powder.

We report the use of terahertz time-domain spectroscopy (THz-TDS) to detect tetracyclines hydrochloride (TCsH) in infant milk powder for the first time. Four kinds of TCsH exhibited their unique spectral features in the region of 0.3-1.8 THz. The main spectral features of these TCsH were still detectable when mixed with infant milk powder with concentrations at 1%-50%, even in the ternary mixtures. The results from chemometrics analysis showed that qualitative and quantitative detection of TCsH in infant milk powder could be successfully achieved. The residual predictive deviation (RPD) values of all these TCsH models were all higher than 2, indicating these models were considered good and could be used in screening purposes. The RPD values of TCH, DTCH, and CTCH models were higher than 3, which were considered excellent for prediction purposes. These preliminary results indicated that THz-TDS combined with chemometrics analysis was suitable for detecting the presence of TCsH residues in a food matrix.

A terahertz metasurface sensor with fingerprint enhancement in a wide spectrum band for thin film detection.

Terahertz spectroscopy is a powerful tool to resolve molecular fingerprints by detecting their vibrational and rotational modes, and has great application potential in chemistry and biomedicine. However, the limited sensitivity and poor specificity restrict its applications in these areas, where trace amounts of analytes need to be identified effectively and accurately. Here, we propose a sensing scheme for enhancing molecular fingerprints based on angle-scanning of terahertz waves on an all-silicon metasurface. The metasurface consists of a periodic array of silicon cylinder dimers arranged in a square lattice. An ultrasharp guided mode resonance governed by bound states in the continuum can be excited by elaborately arranging the silicon cylinder dimers. By utilizing the angle-scanning strategy, two kinds of saccharides are successfully identified with extremely high sensitivity. Specifically, the detection limits for lactose and glucose are 1.53 µg cm-2 and 1.54 µg cm-2, respectively. Our study will provide a new idea for the detection of trace amounts of analytes, and promote the application of terahertz technology in chemistry and biomedicine.

Vibrational spectroscopic detection and analysis of isoniazid-nicotinamide-succinic acid ternary cocrystal.

In this paper, binary and ternary cocrystals in the ternary cocrystal system of isoniazid-nicotinamide-succinic acid were prepared by solvent evaporation and grinding methods. All of them were characterized by terahertz time-domain spectroscopy (THz-TDS), confirming that the cocrystals could be obtained by the above two methods. In addition, to investigate the formation of hydrogen bonds and their influence in cocrystal, several possible forms of hydrogen bond in cocrystal were simulated by density functional theory (DFT). The simulated result was in good agreement with the experimental result, indicating that the hydrogen bonds in cocrystal were the carboxyl groups on both side of succinic acid forming a pyridine N-carboxylic acid heterosynthon with pyridine N of isoniazid or nicotinamide respectively. Meanwhile, the vibrational modes of the cocrystal were analyzed to investigate the effect of hydrogen bond to the molecules. To further understand the formation process of ternary cocrystal in this system, Raman spectroscopy was used to analyze the cocrystal samples with different time of grinding. Process information of cocrystal formation were obtained by analyzing the changes of the characteristic peaks in the corresponding Raman spectra. These results provide a wealth of information and a unique approach to the analysis of both structures and intermolecular interactions shown within ternary cocrystal.

All-metal terahertz metamaterial biosensor for protein detection.

In this paper, a terahertz (THz) biosensor based on all-metal metamaterial is theoretically investigated and experimentally verified. This THz metamaterial biosensor uses stainless steel materials that are manufactured via laser-drilling technology. The simulation results show that the maximum refractive index sensitivity and the figure of merit of this metamaterial sensor are 294.95 GHz/RIU and 4.03, respectively. Then, bovine serum albumin was chosen as the detection substance to assess this biosensor's effectiveness. The experiment results show that the detection sensitivity is 72.81 GHz/(ng/mm2) and the limit of detection is 0.035 mg/mL. This THz metamaterial biosensor is simple, cost-effective, easy to fabricate, and has great potential in various biosensing applications.

Vibrational spectral and structural characterization of multicomponent ternary co-crystal formation within acetazolamide, nicotinamide and 2-pyridone.

Ternary co-crystal, as a novel co-crystal design strategy developed on the basis of binary co-crystal, could be used to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently. However, it is difficult to obtain specific ternary co-crystals since such ternary one involves complex assembly of three different molecules. There are few reports on the micro-molecular structure respect of specific ternary co-crystal systems. In present work, 1:1:1 ternary co-crystal between acetazolamide (ACZ), nicotinamide (NAM) and 2-pyridone (2HP) has been synthesized successfully by mechanical grinding approach, and their structures are investigated by terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy combined with theoretical calculation at the molecular level. The experimental THz spectral results showed that ACZ-NAM-2HP ternary co-crystal and the starting parent materials exhibited a few distinct spectral features in frequency-domain absorption spectra. Likewise, the Raman spectral result also shows some difference between the co-crystal and starting raw materials. Through density functional theory (DFT) calculations, the theoretical THz/Raman spectra and vibrational modes of two kind of possible ternary co-crystal theoretical forms (form I and II) between ACZ, NAM and 2HP were obtained. By comparing experimental and theoretical spectral results, the most suitable structure and vibrational modes of ACZ-NAM-2HP ternary co-crystal were determined. These results provide a wealth of information and unique method for studying molecular assembly and also inter-molecular interactions in specific ternary co-crystals at the molecular level in the emerging pharmaceutical co-crystal fields.

Solid phase drug-drug pharmaceutical co-crystal formed between pyrazinamide and diflunisal: Structural characterization based on terahertz/Raman spectroscopy combining with DFT calculation.

Both pretty low solubility and high membrane permeability of diflunisal (DIF) would affect significantly its oral bioavailability as a typical non-steroidal anti-inflammatory substance. Meanwhile, pyrazinamide (PZA), known as one kind of important anti-tuberculosis drugs, has also several certain side effects. These deficiencies affect the large-scale clinical use of such drugs. Solid-state pharmaceutical co-crystallization is of contemporary interest since it offers an easy and efficient way to produce prospective materials with tunable improved properties. In the current work, a novel solid phase drug-drug co-crystal involving DIF and PZA with molar ratio 1:1 was prepared through the mechanical grinding approach, and vibrational spectroscopic techniques including terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy were performed to identify DIF, PZA and their pharmaceutical drug-drug co-crystal. The absorption peaks observed in the THz spectra of the co-crystal were at 0.35, 0.65, 1.17, 1.31 and 1.42 THz respectively, which are obviously different from parent materials. Similarly, Raman spectra could also be used to characterize the difference shown between the co-crystal and parent compounds. Structures and vibrational patterns of three kinds of possible co-crystal theoretical forms (form I, II and III) between DIF and PZA have been simulated by performing density functional theory (DFT) calculations. Theoretical results and THz/Raman vibrational spectra of DIF-PZA co-crystal show that the DIF links to PZA via the carboxylic acid-pyridine hetero-synthon association establishing the theoretical form I, which is a much-higher degree of agreement with experimental results than those of other two co-crystal forms. These results provide us a unique method for characterizing the composition of co-crystal structures, and also provide a wealth of drug-drug co-crystal structural information for improving physicochemical properties and pharmacological activities of specific drugs at the molecular-level.

Ultrasensitive detection of saccharides using terahertz sensor based on metallic nano-slits.

Unambiguous identification of trace amounts of biochemical molecules in a complex background using terahertz spectroscopy is extremely challenging owing to the extremely small absorption cross sections of these molecules in the terahertz regime. Herein, we numerically propose a terahertz nonresonant nano-slits structure that serves as a powerful sensor. The structure exhibits strongly enhanced electric field in the slits (five orders of magnitude), as well as high transmittance over an extra-wide frequency range that covers the characteristic frequencies of most molecules. Fingerprint features of lactose and maltose are clearly detected using this slits structure, indicating that this structure can be used to identify different saccharides without changing its geometrical parameters. The absorption signal strengths of lactose and maltose with a thickness of 200 nm are strongly enhanced by factors of 52.5 and 33.4, respectively. This structure is very sensitive to thin thickness and is suitable for the detection of trace sample, and the lactose thickness can be predicted on the basis of absorption signal strength when the thickness is less than 250 nm. The detection of a mixture of lactose and maltose indicates that this structure can also achieve multi-sensing which is very difficult to realize by using the resonant structures.

Structural insights into anhydrous and monohydrated forms of 2,4,6-trihydroxybenzoic acid based on Raman and terahertz spectroscopic characterization.

In order to characterize molecular structures of 2,4,6-trihydroxybenzoic acid (PCA) by means of vibrational spectroscopic techniques, we report investigation of PCA monohydrated form and its anhydrous polymorphic one by using terahertz and Raman spectral characterization. The experimental THz spectra show that the monohydrated PCA only has two absorption bands at 0.69 and 1.65 THz respectively in the frequency region from 0.2 to 1.8 THz, meanwhile the anhydrous form has a few significantly different absorption bands at 0.75, 1.01, 1.46 and 1.64 THz, respectively. Furthermore, Raman spectra characterized such differences of vibrational modes shown within 200-1800 cm-1 region about the monohydrated and anhydrous forms of PCA. In view of various possible theoretical structural forms that may exist in anhydrous PCA and its monohydrated one, density functional theory calculations were performed to simulate optimized structures and vibrational mode of above two PCA polymorphic forms. Theoretical results and experimental THz/Raman spectra of anhydrous PCA show that the dimer synthon via the carboxylic group ••• carboxyl group and its ortho-phenolic hydroxyl group inter-molecular hydrogen bonding interaction establishing the theoretical form I (AH-I) is more consistent with experimental observation than other theoretical forms (AH-II and AH-III). Meanwhile, the theoretical monohydrated form I (MH-I), which is formed by the linkage of carboxyl group and its ortho-phenolic hydroxyl group with water molecule, is also much more agreement with experimental spectral observations of PCA monohydrate than other monohydrated forms (MH-II and MH-III). Our study demonstrates effectively qualitative analysis of both micro-molecular structures and dehydrated transitions between anhydrous and hydrated polymorphic forms of PCA, thus providing rich information on the corresponding structural changes of anhydrous and hydrated PCAs due to various inter-molecular and intra-molecular interactions based on their finger-print vibrational spectra combined with theoretical simulations.

Rapid in situ analysis of l-histidine and α-lactose in dietary supplements by fingerprint peaks using terahertz frequency-domain spectroscopy.

A simple, green and nondestructive method based on terahertz fingerprint peaks has been developed for rapid in situ analysis of l-histidine and α-lactose in dietary supplements. Fingerprint absorption peaks of l-histidine and α-lactose located at 0.77 and 0.53 THz could be directly used for identification and quantitation of these analytes in commercial dietary supplements. Compared with the partial least squares regression model (PLSR), the linear least squares regression (LLSR) method based on peak areas presented better performance, with the linear correlation coefficients of 0.9899 and 0.9910 for l-histidine and α-lactose, respectively. Furthermore, analysis time per sample can be shortened to less than 1 min due to the narrower spectral acquisition region. The accuracies were 94.8-110% and 98.9-110%, comparable to those of ion chromatography for l-histidine and high-performance liquid chromatography for α-lactose. The results presented great potential of the developed method for rapid in situ analysis of nutrients in dietary supplements.

Structure and spectroscopic characterization of pharmaceutical co-crystal formation between acetazolamide and 4-hydroxybenzoic acid.

Co-crystals have great potential for drug research and development because the formation of co-crystal is accompanied by changes inter-molecular interactions between starting materials that enable to improve both physical and chemical properties of active pharmaceutical ingredients. In order to provide a more profound insight into the structural changes of specific drugs upon co-crystallization, spectroscopic characterization of solid-state acetazolamide (ACZ), 4-hydroxybenzoic acid (4HBA) and their co-crystal prepared by mechanical grinding approach has been performed with spectral techniques including terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy. Experimental THz spectra show that the ACZ-4HBA co-crystal has a few significantly different absorption peaks in 0.82, 1.16, 1.28 and 1.64 THz respectively compared with parent materials in the frequency region from 0.2 to 1.8 THz. Likewise, such differences between the co-crystal and starting compounds could also be characterized by Raman vibrational spectra. Moreover, density functional theory (DFT) calculations were performed to simulate optimized structures and vibrational modes of three kind of possible co-crystal theoretical forms (form I, II and III) between ACZ and 4HBA. Theoretical results and THz/Raman vibrational spectra of ACZ-4HBA co-crystal show that the 4HBA links to the thiadiazole acetamide fragment of ACZ via the double-bridged heterodimeric synthon C(N)NH⋯HOOC inter-molecular hydrogen bonding interaction establishing the theoretical form I, which is more consistent with experimental observations than other two possible theoretical co-crystal forms. These results provide rich information and unique method for characterizing the composition of co-crystal structures and also inter-molecular interactions shown within pharmaceutical co-crystallization process at the molecular level.

A sensitive and selective terahertz sensor for the fingerprint detection of lactose.

Special recognition to molecules is essential for many biochemical processes, thus highly sensitive sensing methods for molecule recognition are strongly demanded. Recently, metamaterials present a unique platform for sensing applications owing to their exotic properties. In the current work, a metamaterial sensor for enhanced fingerprint detection of lactose based on resonant coupling of plasmonic modes of split-ring resonators (SRRs) and terahertz characteristic modes of lactose was theoretically and experimentally demonstrated. Large electric field enhancement (about 120 times) at the gap of SRRs allows for the highly sensitive detection. A narrow transmittance peak in the broader transmittance dip which corresponded to the characteristic modes of lactose was observed due to the resonant coupling, and the differential transmittance enhanced as the lactose concentration increased. The experimental result agreed well with the theoretical analysis. Moreover, the selectivity of this SRRs sensor for the target molecule was also verified by using fructose. A low amount of lactose, as small as 20 mg/mL was successfully detected in the experiment. Our study opens a new avenue to exploit new materials or devices for molecule sensing with high sensitivity and selectivity.

Co-Crystal Formation of Antibiotic Nitrofurantoin Drug and Melamine Co-Former Based on a Vibrational Spectroscopic Study.

The co-crystallization of active pharmaceutical ingredients (APIs) has received increasing attention due to the modulation of the relative physicochemical properties of APIs such as low solubility, weak permeability and relatively inferior oral bioavailability. Crystal engineering plays a decisive role in the systematic design and synthesis of co-crystals by means of exerting control on the inter-molecular interactions. The characterization and detection of such co-crystal formations plays an essential role in the field of pharmaceutical research and development. In this work, nitrofurantoin (NF), melamine (MELA) and their hydrated co-crystal form were characterized and analyzed by using terahertz time-domain spectroscopy (THz-TDS) and Raman vibrational spectroscopy. According to the experimental THz spectra, the hydrated co-crystal form has characteristic absorption peaks at 0.67, 1.05, 1.50 and 1.73 THz, while the THz spectra for the two raw parent materials (NF and MELA) are quite different within this spectral region. Similar observations were made from the experimental Raman vibrational spectra results. Density functional theory (DFT) calculation was performed to help determine the major vibrational modes of the hydrated co-crystal between nitrofurantoin and melamine, as well as identify the structural changes due to inter- and/or intra-molecular hydrogen bonding motifs between NF and MELA. The results of the theoretical frequency calculations corroborate the THz and Raman experimental spectra. The characteristic bands of the NF⁻MELA-hydrated co-crystal between nitrofurantoin and melamine were also determined based on the DFT simulated calculation. The reported results in this work provide us with a wealth of structural information and a unique vibrational spectroscopic method for characterizing the composition of specific co-crystals and inter-molecular hydrogen bonding interactions upon pharmaceutical co-crystallization.